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To determine the perioperative characteristics associated with an increased risk of postoperative urinary retention (POUR) following vaginal pelvic floor surgery.A retrospective cohort study using multivariable prediction modelling.A tertiary referral urogynaecology unit.Patients undergoing vaginal pelvic floor surgery from January 2015 to February 2020.Eighteen variables (24 parameters) were compared between those with and without POUR and then included as potential predictors in statistical models to predict POUR. The final model was chosen as the model with the largest concordance index (c-index) from internal cross-validation. This was then externally validated using a separate data set (n = 94) from another surgical centre.Diagnosis of POUR following surgery while the patient was in hospital.Among the 700 women undergoing surgery, 301 (43%) experienced POUR. Preoperative variables with statistically significant univariate relationships with POUR included age, menopausal status, prolapse stage and uroflowmetry parameters. Significant perioperative factors included estimated blood loss, volume of intravenous fluid administered, operative time, length of stay and specific procedures, including vaginal hysterectomy with intraperitoneal vault suspension, anterior colporrhaphy, posterior colporrhaphy and colpocleisis. The lasso logistic regression model had the best combination of internally cross-validated c-index (0.73, 95% CI 0.71-0.74) and a calibration curve that showed good alignment between observed and predicted risks. Using this data, a POUR risk calculator was developed (https://pourrisk.shinyapps.io/POUR/).This POUR risk calculator will allow physicians to counsel patients preoperatively on their risk of developing POUR after vaginal pelvic surgery and help focus discussion around potential management options.

Patients with Parkinson's disease might develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation.To study whether lateralized stimulation (unilateral 50% amplitude reduction) for ≥21 days results in ≥0.13 m/s faster gait velocity in the dopaminergic ON state in these patients, and its effects on motor and axial function, quantitative gait and speech measures, quality of life, and selected cognitive tasks.Randomized, double-blinded, double-crossover trial.In 22 participants (51-79 years old, 15 women), there were no significant changes in gait velocity, quality of life, cognitive, and speech measures. Reducing left-sided amplitude resulted in a 2.5-point improvement in axial motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (P = 0.005, uncorrected) and a 1.9-point improvement in the Freezing of Gait Questionnaire (P = 0.024, uncorrected).Lateralized subthalamic stimulation does not result in meaningful improvement in gait velocity in patients with Parkinson's disease who develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. Left subthalamic overstimulation may contribute to axial deterioration in these patients. © 2022 International Parkinson and Movement Disorder Society.

Summary We aimed to identify risk factors for adverse outcomes in pregnancies of women with sickle cell disease (SCD) and develop risk prediction models. Models were derived from a retrospective cohort of pregnant women with SCD and constructed using generalised estimating equation logistic regression, with clustering by woman. Maternal event(s) consisted of acute anaemia; cardiac, pulmonary, hepatobiliary, musculoskeletal, skin, splenic, neurological or renal complications, multi‐organ failure, venous thromboembolism, admission‐requiring vaso‐occlusive events (VOE), red cell transfusion, mortality or hypertensive disorder of pregnancy. Fetal events included preterm birth, small‐for‐gestational‐age or perinatal mortality. Of 199 pregnancies, 71% and 45% resulted in adverse maternal and fetal outcomes respectively. Low first‐trimester haemoglobin, admission‐requiring VOE in the year before pregnancy, multiple transfusions before pregnancy, SCD genotype and previous cardiac complications predicted maternal risk. Younger age and SCD genotype allowed early prediction of fetal risk (model‐F1). Adding maternal event(s) and high lactate dehydrogenase enabled re‐assessment of fetal risk with advancing gestation (model‐F2). Models were well calibrated and moderately discriminative for maternal outcome (c‐statistic 0·81, cross‐validated value 0·79) and fetal outcome (model‐F1 c‐statistic 0·68, cross‐validated value 0·65; model‐F2 c‐statistic 0·72, cross‐validated value 0·68). The models will allow early identification of women with SCD at high risk of adverse events, permitting early targeted interventions and ongoing fetal risk re‐assessment enabling intensification of surveillance and optimisation of delivery timing.

BACKGROUND Because multiple treatments are available for metastatic castrate-resistant prostate cancer (mCRPC) and most patients are elderly, the prediction of toxicity risk is important. The Cancer and Aging Research Group (CARG) tool predicts chemotherapy toxicity in older adults with mixed solid tumors, but has not been validated in mCRPC. In this study, its ability to predict toxicity risk with docetaxel chemotherapy (CHEMO) was validated, and its utility was examined in predicting toxicity risk with abiraterone or enzalutamide (A/E) among older adults with mCRPC. METHODS Men aged 65+ years were enrolled in a prospective observational study at 4 Canadian academic cancer centers. All clinically relevant grade 2 to 5 toxicities over the course of treatment were documented via structured interviews and chart review. Logistic regression was used to identify predictors of toxicity. RESULTS Seventy-one men starting CHEMO (mean age, 73 years) and 104 men starting A/E (mean age, 76 years) were included. Clinically relevant grade 3+ toxicities occurred in 56% and 37% of CHEMO and A/E patients, respectively. The CARG tool was predictive of grade 3+ toxicities with CHEMO, which occurred in 36%, 67%, and 91% of low, moderate, and high-risk groups (P = .003). Similarly, grade 3+ toxicities occurred among A/E users in 23%, 48%, and 86% with low, moderate, and high CARG risk (P < .001). However, it was not predictive of grade 2 toxicities with either treatment. CONCLUSIONS There is external validation of the CARG tool in predicting grade 3+ toxicity in older men with mCRPC undergoing CHEMO and demonstrated utility during A/E therapy. This may aid with treatment decision-making.

BACKGROUND Our study assessed post-radiation therapy (RT) G-tube presence, duration, and clinical predictors in patients with head and neck cancer (HNC). METHODS We identified those 1-5-years post-RT with stage III/IV nasopharyngeal, oropharyngeal, hypopharyngeal, laryngeal, or unknown primaries. Logistic regression identified predictors of post-RT G-tube presence, Kaplan-Meier analysis estimated G-tube days, and log-rank test compared by tumor site. RESULTS The 977 patients had mean age 60.6 ± 11.6 years, 804 (82.3%) male, 764 (78.2%) stage IV, and 618 (63.3%) oropharyngeal primaries. All patients received intensity-modulated RT (IMRT), 571 (58.4%) received chemotherapy, and 698 (71.4%) prophylactic G-tube. G-tube prevalence 1- and 5-years post-IMRT was 7.1% and 4.8%, respectively. Median post-IMRT G-tube days were overall 63 (95%CI: 56-70), nasopharynx 119 (95%CI: 109-131), oropharynx 57 (95%CI: 51-68), hypopharynx 126 (95%CI: 77-256), larynx 53 (95%CI: 21-63), unknown 30 (95%CI: 17-55), of which hypopharynx was highest p

Aims: This study aimed to review the performance of machine learning (ML) methods compared with conventional statistical models (CSMs) for predicting readmission and mortality in patients with heart failure (HF) and to present an approach to formally evaluate the quality of studies using ML algorithms for prediction modelling. Methods and results: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic literature search using MEDLINE, EPUB, Cochrane CENTRAL, EMBASE, INSPEC, ACM Library, and Web of Science. Eligible studies included primary research articles published between January 2000 and July 2020 comparing ML and CSMs in mortality and readmission prognosis of initially hospitalized HF patients. Data were extracted and analysed by two independent reviewers. A modified CHARMS checklist was developed in consultation with ML and biostatistics experts for quality assessment and was utilized to evaluate studies for risk of bias. Of 4322 articles identified and screened by two independent reviewers, 172 were deemed eligible for a full-text review. The final set comprised 20 articles and 686842 patients. ML methods included random forests (n=11), decision trees (n=5), regression trees (n=3), support vector machines (n=9), neural networks (n=12), and Bayesian techniques (n=3). CSMs included logistic regression (n=16), Cox regression (n=3), or Poisson regression (n=3). In 15 studies, readmission was examined at multiple time points ranging from 30 to 180day readmission, with the majority of studies (n=12) presenting prediction models for 30day readmission outcomes. Of a total of 21 time-point comparisons, ML-derived c-indices were higher than CSM-derived c-indices in 16 of the 21 comparisons. In seven studies, mortality was examined at 9 time points ranging from in-hospital mortality to 1year survival; of these nine, seven reported higher c-indices using ML. Two of these seven studies reported survival analyses utilizing random survival forests in their ML prediction models. Both reported higher c-indices when using ML compared with CSMs. A limitation of studies using ML techniques was that the majority were not externally validated, and calibration was rarely assessed. In the only study that was externally validated in a separate dataset, ML was superior to CSMs (c-indices 0.913 vs. 0.835). Conclusions: ML algorithms had better discrimination than CSMs in most studies aiming to predict risk of readmission and mortality in HF patients. Based on our review, there is a need for external validation of ML-based studies of prediction modelling. We suggest that ML-based studies should also be evaluated using clinical quality standards for prognosis research. Registration: PROSPERO CRD42020134867.

Objective The economic burden of childhood epilepsy to the health care system remains poorly understood. This study aimed to determine phase-specific and cumulative long-term health care costs in children with epilepsy (CWE) from the health care payer perspective. Methods This cohort study utilized linked health administrative databases in Ontario, Canada. Incident childhood epilepsy cases were identified from January 1, 2003 to June 30, 2017. CWE were matched to children without epilepsy (CWOE) on age, sex, rurality, socioeconomic status, and comorbidities, and assigned prediagnosis, initial, ongoing, and final care phase based on clinical trajectory. Phase-specific, 1-year and 5-year cumulative health care costs, attributable costs of epilepsy, and distribution of costs across different ages were evaluated. Results A total of 24 411 CWE were matched to CWOE. The costs were higher for prediagnosis and initial care than ongoing care in CWE. Hospitalization was the main cost component. The costs of prediagnosis, initial, and ongoing care were higher in CWE than CWOE, with the attributable costs at $490 (95% confidence interval [CI] = $352-$616), $1322 (95% CI = $1247-$1402), and $305 (95% CI = $276-$333) per 30 patient-days, respectively. Final care costs were lower in CWE than CWOE, with attributable costs at -$2515 (95% CI = -$6288 to $961) per 30 patient-days. One-year and 5-year cumulative costs were higher in CWE ($14 776 [95% CI = $13 994-$15 546] and $39 261 [95% CI = $37 132-$41 293], respectively) than CWOE ($6152 [95% CI = $5587-$6768] and $15 598 [95% CI = $14 291-$17 006], respectively). The total health care costs were highest in the first year of life in CWE for prediagnosis, initial, and ongoing care. Significance Health care costs varied along the continuum of epilepsy care, and were mainly driven by hospitalization costs. The findings identified avenues for remediation, such as enhancing care around the time of epilepsy diagnosis and better care coordination for epilepsy and comorbidities, to reduce hospitalization costs and the economic burden of epilepsy care.

Objective To determine the contribution of rheumatoid arthritis (RA) to conditions and medical events. A secondary objective is to quantify this association before and after the introduction of biologic medications. Methods All data were collected as health administrative data in Ontario, Canada. Patients with RA (n = 136 678) matched 1:1 to a pool of possible controls without RA from 1995 to 2016. The study was a retrospective longitudinal observational administrative data-based cohort study with cases (RA) and controls (two non-RA comparator groups). The main exposure was new-onset RA identified by a validated diagnosis algorithm. The secondary exposure was the calendar year, which provided a natural experiment to compare years in which biologics were unavailable (pre-2001) to increasing utilization over time. The main outcomes were counts of 27 Johns Hopkins Expanded Diagnostic Cluster Comorbid Conditions. Outcomes were reported as counts and percentage differences between cases and matched controls. Results Patients experienced increases in conditions and medical events up to 5 years before RA disease incidence-4.9 conditions per patient-year compared with 4.6 conditions per patient-year in matched controls. Comorbidities increased to 8.7 conditions per patient-year in the year of RA incidence but were lower in the years after diagnosis-6.9 conditions per patient-year at 5 years postdiagnosis. Conclusion This study reframes the clinical manifestations of RA with detailed data on the marginal contribution of RA to conditions and medical events. These results show that a large portion of disease burden is due to the indirect effects of RA.

Objective The relationship between physical activity (PA) and quality of life (QOL) relative to active treatment for prostate cancer (PCa) has been well-studied; however, little is known about this relationship during active surveillance (AS). Moreover, whether PA is associated with better emotional well-being (EWB) in men with low-risk PCa requires further investigation. Accordingly, we examined the association between self-reported PA and the average change in QOL and EWB over time during AS. Methods A total of 630 men on AS were included in this retrospective, longitudinal study from AS initiation until AS discontinuation. Generalized estimated equations were used to determine the association between self-reported PA (independent variable) and QOL and EWB (dependent variables) over time, adjusting for participants' age. Results QOL was higher over time in active ( β ^ (95%CI) = 1.14 (0.11, 2.16), P = .029) and highly active participants ( β ^ (95%CI) = 1.62 (0.58, 2.67), P = .002) compared to their inactive counterparts. Highly active participants had 55% greater odds of experiencing high EWB relative to inactive participants (OR (95%CI) = 1.55 (1.11, 2.16), P = .010). In men with low EWB at baseline (median = 3 months after diagnosis), the highest levels of PA (>1000 metabolic equivalent-minutes per week) were associated with high EWB over time (OR (95%CI) = 2.17 (1.06, 4.46), P = .034). Conclusions These data further support the importance of PA as a supportive care strategy for men on AS. Our findings suggest that engaging in higher volumes of PA post-diagnosis may be beneficial particularly for men exhibiting low emotional well-being early on during AS.

Post-transplant diabetes mellitus (PTDM) compromises long-term survival in liver transplant (LT) recipients. The aim of this study was to determine incidence of PTDM after LT and risk factors associated with it. A literature search was conducted, and prospective studies that reported on the incidence of PTDM in LT adult patients on tacrolimus, sirolimus, or cyclosporine were included. We performed random effects meta-analyses for the incidence of PTDM stratified by immunosuppressant and time period. Of 9817 articles identified, 26 studies were included in the qualitative analysis and 21 studies were eligible for the quantitative analysis representing 79 559 LT recipients in 32 separate treatment arms. The proportion of patients who developed PTDM by two-three years was 0.15 (95% CI: 0.10-0.24) for cyclosporine, 0.23 (95% CI: 0.14-0.36) for tacrolimus, and 0.27 (95% CI: 0.23-0.30) for sirolimus. CONCLUSION: Our results showed that sirolimus-based immunosuppression was associated with a higher incidence of PTDM than tacrolimus or cyclosporine at two-three years. However, there were only two studies that compared all three drugs which is a limitation of the study and requires more studies with patients on sirolimus. Recipient factors increasing the risk of PTDM are older age, male sex, and high BMI.

PURPOSE To determine the efficacy and safety of different prophylactic systemic antibiotics in adult and pediatric patients receiving chemotherapy or undergoing hematopoietic stem cell transplantation (HSCT). METHODS We conducted a systematic review and performed searches of Ovid MEDLINE, MEDLINE in-process and Embase; and Cochrane Central Register of Controlled Trials. Studies were included if patients had cancer or were HSCT recipients with anticipated neutropenia, and the intervention was systemic antibacterial prophylaxis. Strategies synthesized included fluoroquinolone vs no antibiotic/nonabsorbable antibiotic; fluoroquinolone vs trimethoprim-sulfamethoxazole; trimethoprim-sulfamethoxazole vs no antibiotic; and cephalosporin vs. no antibiotic. Fluoroquinolone vs cephalosporin and levofloxacin vs ciprofloxacin were compared by network meta-analysis. Primary outcome was bacteremia. RESULTS Of 20 984 citations screened, 113 studies comparing prophylactic antibiotic to control were included. The following were effective in reducing bacteremia: fluoroquinolone vs no antibiotic/nonabsorbable antibiotic (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.41-0.76), trimethoprim-sulfamethoxazole vs no antibiotic (RR 0.59, 95% CI 0.41-0.85) and cephalosporin vs no antibiotic (RR 0.30, 95% CI 0.16-0.58). Fluoroquinolone was not significantly associated with increased Clostridium difficile infection (RR 0.62, 95% CI 0.31-1.24) or invasive fungal disease (RR 1.28, 95% CI 0.79-2.08) but did increase resistance to fluoroquinolone among bacteremia isolates (RR 3.35, 95% CI 1.12 to 10.03). Heterogeneity in fluoroquinolone effect on bacteremia was not explained by evaluated study, population, or methodological factors. Network meta-analysis revealed no direct comparisons for pre-specified analyses; superior regimens were not identified. CONCLUSIONS Fluoroquinolone, trimethoprim-sulfamethoxazole, and cephalosporin prophylaxis reduced bacteremia. A clinical practice guideline to facilitate prophylactic antibiotic decision-making is required.

While doses of deferiprone up to 75 mg/kg/d have been demonstrated to be effective in cardiac iron removal, their efficacy in the reduction of liver iron has been equivocal. The aim of this study was to evaluate the effect of deferiprone dose on liver iron concentrations in adult iron overload patients.A single-centered, retrospective, cohort observational study was conducted involving 71 patients exposed to deferiprone doses up to 113 mg/kg/d between January 2009 and June 2015 for a median of 33 months.At the end of the study period, liver iron measured by R2 MRI was reduced by a mean 1.7 mg/g dw. A dose effect was observed, with incremental reductions of 2.8 mg/g dw in end of study LIC for every 10 mg/kg/d higher dose of deferiprone (P 0.001). A dose effect was also observed in end of study ferritin and cardiac iron concentration measured by T2* MRI (P 0.0001 and P = 0.048, respectively). No associations between adverse effects and deferiprone dose were observed, but there was a trend toward higher rates of agranulocytosis at higher doses and two of three hereditary hemochromatosis patients developed this complication.The present study failed to demonstrate that the use of deferiprone at90 mg/kg/d was associated with increased risk of agranulocytosis or neutropenia, but did demonstrate more effective liver iron control in iron overload patients.

BACKGROUND QRS abnormalities may not be apparent in sinus rhythm in electrically stable cardiomyopathy patients who can have quiescent but highly arrhythmogenic substrate. Here, we test the hypothesis that differential changes in QRS construction during right-ventricular apex pacing (RVP) as opposed to atrial pacing (AP) will identify latent substrate for ventricular arrhythmias (VA) and death. METHODS Forty patients with cardiomyopathy free of VA underwent baseline 114-electrode body-surface electrocardiogram during AP (100 beats per minute [bpm]) and RVP (100 and 120 bpm). The filtered-averaged QRS at each electrode was deconstructed into individual intra-QRS and post-QRS ventricular myopotentials (VMP ). The primary outcome was VA or death. Prognostic accuracy of VMP was validated using V1 to V6 leads in another prospective cohort of 44-cardiomyopathy patients. RESULTS Twenty-six patients were eligible for initial analysis. After 5 ± 2 years of follow-up, eight (31%) patients had VA (VAPos ) while rest were uneventful (VANeg ). During AP100 , VAPos patients expressed more VMP than VANeg patients (16 ± 1 vs 12 ± 1, P = 0.02). RVP100 and RVP120 in VAPos patients introduced an additional 5.5 ± 0.5 and 6.0 ± 0.5 VMP (P

RATIONALE Cytomegalovirus (CMV)-seronegative recipients receiving a seropositive allograft (D+/R-) are at a high risk of developing CMV disease. Our program increased the duration of CMV prophylaxis from 6 to 9 months in May 2013. Here, we present the impact on the incidence of CMV infection, disease, side effects, rejection, and other factors. METHODS Retrospective cohort of 241 CMV (D+/R-) patients transplanted between January 1, 2008, and December 31, 2017. Blood CMV testing was done according to protocol. All patients received ganciclovir/valganciclovir as prophylaxis. We compared the incidence and timing of CMV infection and disease up to 6 months after cessation of prophylaxis between patients who received 9 months (May 2013 onwards) and a historical control group who received 6 months of prophylaxis (prior to May 2013). CMV infection was defined as detectable CMV viremia in the absence of symptoms. CMV disease was defined as CMV syndrome or tissue-invasive disease. Side effects of prophylaxis and CMV resistance were recorded. RESULTS A total of 116 patients were included in the 6-month group and 125 in the 9-month group. The extended 9-month CMV prophylaxis delayed the onset of CMV infection (median time to CMV infection after lung transplantation 295 vs 353 days, P

The pediatric rheumatic diseases are a heterogeneous group of rare diseases, posing a number of challenges for the use of traditional clinical and translational research methods. Innovative comparative effectiveness approaches are needed to efficiently study treatment strategies and disease outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed the consensus treatment plan (CTP) approach as a comparative effectiveness tool for research in pediatric rheumatology. CTPs are treatment strategies, developed by consensus methods among CARRA members, intended to reduce variation in treatment approaches, standardize outcome measurements, and allow for comparison of the effectiveness of different approaches with the goal of improving disease outcomes. To date, CTPs have been published for 8 different diseases and disease manifestations. The approach has been successfully piloted for juvenile localized scleroderma, systemic juvenile idiopathic arthritis (JIA), polyarticular JIA, dermatomyositis, and lupus nephritis. Large-scale studies are underway for systemic JIA and polyarticular JIA, with the CARRA patient registry serving as the data collection platform. These studies have been designed with stakeholder involvement, including active input from CARRA providers, patients, and parents, with the goal of increasing feasibility and ensuring the relevance of the outcomes. These studies include ancillary biologic specimen collection intended to support additional translational and mechanistic studies. Data from these ongoing CTP studies will provide more information on the ability of this approach to identify effective treatment strategies and improve outcomes in the pediatric rheumatic diseases.

Objectives were to describe any bothersome symptom and severely bothersome symptoms in inpatient children with cancer and hematopoietic stem cell transplant (HSCT) recipients. We included children 8–18 years of age with cancer or HSCT recipients who were receiving active treatment for cancer, admitted to hospital, and expected to be in hospital 3 days later. We administered the self‐report Symptom Screening in Pediatrics Tool (SSPedi). We described those who identified any degree of symptom bother (at least “a little”) and those who rated the degree of bother as severe (“a lot” or “extremely”). Factors associated with severe symptoms and total SSPedi scores were examined using multiple logistic and linear regression. Among the 302 patients, 298 (98.7%) reported having any bothersome symptom and 181 (59.9%) had at least one severely bothersome symptom. In multiple regression, older children were significantly more likely to have at least one severely bothersome symptom (15–18 and 11–14 years vs. 8–10 years; P = 0.008) and to have higher total SSPedi scores (P = 0.0003). Those with relapsed disease were more likely to have at least one severely bothersome symptom (odds ratio 2.1, 95% confidence interval 1.1–4.3; P = 0.037) and HSCT recipients were more likely to have higher symptom scores (β = 3.48, standard error = 1.6; P = 0.030). Almost all children receiving cancer therapies experience bothersome symptoms and 60% have at least one severely bothersome symptom. Older children experienced more severely bothersome symptoms and higher symptom scores. Future studies should follow children longitudinally to better understand the symptom trajectory and should institute interventions to manage symptoms.

BACKGROUND Strategies to improve bone health care in men receiving androgen deprivation therapy (ADT) are not consistently implemented. The authors conducted a phase 2 randomized controlled trial of 2 education-based models-of-care interventions to determine their feasibility and ability to improve bone health care. METHODS A single-center parallel-group randomized controlled trial of men with prostate cancer who were receiving ADT was performed. Participants were randomized 1:1:1 to 1) a patient bone health pamphlet and brief recommendations for their family physician (BHP+FP); 2) a BHP and support from a bone health care coordinator (BHP+BHCC); or 3) usual care. The primary efficacy outcome was receipt of a bone mineral density (BMD) test within 6 months. Secondary efficacy outcomes included guideline-appropriate calcium and vitamin D use and bisphosphonate prescriptions for men at high fracture risk. Feasibility endpoints included recruitment, retention, satisfaction, contamination, and outcome capture. The main analysis used logistic regression with a 1-sided P of .10. The trial is registered at ClinicalTrials.gov (identifier NCT02043236). RESULTS A total of 119 men were recruited. The BHP+BHCC strategy was associated with a greater percentage of men undergoing a BMD test compared with the usual-care group (78% vs 36%; P

Introduction Both types of sleep-disordered breathing (SDB), obstructive and central sleep apnoea (OSA and CSA, respectively), are common in patients with heart failure and reduced ejection fraction (HFrEF). In such patients, SDB is associated with increased cardiovascular morbidity and mortality but it remains uncertain whether treating SDB by adaptive servo-ventilation (ASV) in such patients reduces morbidity and mortality. Aim ADVENT-HF is designed to assess the effects of treating SDB with ASV on morbidity and mortality in patients with HFrEF. Methods ADVENT-HF is a multicentre, multinational, randomized, parallel-group, open-label trial with blinded assessment of endpoints of standard medical therapy for HFrEF alone vs. with the addition of ASV in patients with HFrEF and SDB. Patients with a history of HFrEF undergo echocardiography and polysomnography. Those with a left ventricular ejection fraction ≤45% and SDB (apnoea–hypopnoea index ≥15) are eligible. SDB is stratified into OSA with ≥50% of events obstructive or CSA with >50% of events central. Those with OSA must not have excessive daytime sleepiness (Epworth score of ≤10). Patients are then randomized to receive or not receive ASV. The primary outcome is the composite of all-cause mortality, cardiovascular hospital admissions, new-onset atrial fibrillation requiring anti-coagulation but not hospitalization, and delivery of an appropriate discharge from an implantable cardioverter-defibrillator not resulting in hospitalization during a maximum follow-up time of 5 years. Conclusion The ADVENT-HF trial will help to determine whether treating SDB by ASV in patients with HFrEF improves morbidity and mortality.

Evidence-based medicine requires strong scientific evidence upon which to base treatment. In rare diseases, study populations are often small, and thus this evidence is difficult to accrue. Investigators, though, should be creative and develop a flexible toolkit of methods to deal with the problems inherent in the study of rare disease. This narrative review presents alternative clinical trial designs for studying treatments of rare diseases, including cross-over and n-of-1 trials, randomized placebo-phase design, enriched enrollment, randomized withdrawal design, and classes of adaptive designs. Examples of applications of these designs are presented along with their advantages and disadvantages. Additional analytical considerations such as Bayesian analysis, internal pilots, and use of biomarkers as surrogate outcomes are further discussed. A framework for selecting appropriate clinical trial design is proposed to guide investigators in the process of selecting alternative designs for rare diseases. © 2016 Wiley Periodicals, Inc.

Bivariate random-effects meta-analysis (BVMA) is a method of data synthesis that accounts for treatment effects measured on two outcomes. BVMA gives more precise estimates of the population mean and predicted values than two univariate random-effects meta-analyses (UVMAs). BVMA also addresses bias from incomplete reporting of outcomes. A few tutorials have covered technical details of BVMA of categorical or continuous outcomes. Limited guidance is available on how to analyze datasets that include trials with mixed continuous-binary outcomes where treatment effects on one outcome or the other are not reported. Given the advantages of Bayesian BVMA for handling missing outcomes, we present a tutorial for Bayesian BVMA of incompletely reported treatment effects on mixed bivariate outcomes. This step-by-step approach can serve as a model for our intended audience, the methodologist familiar with Bayesian meta-analysis, looking for practical advice on fitting bivariate models. To facilitate application of the proposed methods, we include our WinBUGS code. As an example, we use aggregate-level data from published trials to demonstrate the estimation of the effects of vitamin K and bisphosphonates on two correlated bone outcomes, fracture, and bone mineral density. We present datasets where reporting of the pairs of treatment effects on both outcomes was 'partially' complete (i.e., pairs completely reported in some trials), and we outline steps for modeling the incompletely reported data. To assess what is gained from the additional work required by BVMA, we compare the resulting estimates to those from separate UVMAs. We discuss methodological findings and make four recommendations. Copyright © 2015 John Wiley & Sons, Ltd.

Objective To evaluate excess mortality over time, comparing rheumatoid arthritis (RA) patients with the general population. Methods We computed all-cause mortality rates among Ontario residents age ≥15 years with RA versus without RA from 1996 to 2009. Age- and sex-standardized mortality rates were expressed as the number of deaths per 1,000 population. Excess mortality rates were calculated as the difference between death rates among RA patients and those in the general population. We estimated standardized mortality ratios (SMRs) and mortality rate ratios (MRRs) to assess relative excess mortality over time. Results From 1996 to 2009, SMRs in RA ranged from 13.0 (95% confidence interval [95% CI] 12.2, 13.9) to 9.2 deaths per 1,000 RA patients (95% CI 8.4, 10.0); and for those without RA from 8.7 (95% CI 8.6, 8.7) to 6.0 deaths (95% CI 5.9, 6.0) per 1,000 general population. Over the study period, the excess mortality rate among RA patients was approximately 3 excess deaths per 1,000 population. Relative reductions in standardized mortality rates occurred over time for those with and without RA (−21.4% versus −13.4%). The SMRs for RA patients in 1996–1997, 2000–2001, 2004–2005, and 2008–2009 were 1.51 (95% CI 1.43, 1.59), 1.50 (95% CI 1.43, 1.57), 1.43 (95% CI 1.37, 1.50), and 1.41 (95% CI 1.35, 1.47), respectively. We did not find a significant change in the MRR by calendar time. Conclusion Mortality for RA patients has decreased over time but remains elevated compared to the general population, with 40–50% more deaths among RA patients. The relative excess mortality over time (mortality gap) remains unchanged in our sample.

BACKGROUND This study examined the impact of androgen-deprivation therapy (ADT) on physical function and quality of life (QOL) over 36 months. METHODS Eighty-seven men with nonmetastatic prostate cancer (PC) who were starting continuous ADT and 2 control groups (86 PC controls without ADT and 86 healthy controls), matched by age and education, were enrolled. Physical function was assessed with the 6-minute walk test (6MWT), grip strength, and Timed Up and Go (TUG) test. QOL was measured with the 36-Item Short Form Health Survey of the Medical Outcomes Study. Subjects were assessed at the baseline and at 3, 6, 12, 18, 24, 30, and 36 months. Mixed effects regression models were fitted with adjustments for baseline covariates. RESULTS The 6MWT distance improved initially and then stabilized in both control groups but remained unchanged for ADT users (P = .0030). Grip strength remained stable in control groups but declined sharply in the ADT group by 3 months and then remained stable to 36 months (P = .0041). TUG scores declined gradually in the ADT group over 36 months but were unchanged in control groups (P = .0008). Aggregate physical QOL declined in ADT users over time but remained stable in control groups (P = .0001). Aggregate mental QOL was stable in all groups. Declines seen in the first year of ADT use generally persisted over 36 months and were independent of age. CONCLUSIONS Previously noted physical side effects over the first 12 months of ADT persisted or continued to worsen over an additional 2 years with no evidence of recovery. Exercise interventions to counteract these declines may be warranted. Cancer 2015;121:2350–2357. © 2015 American Cancer Society.

Objective To assess whether radical nephrectomy (RN) compared with partial nephrectomy (PN) for the treatment of renal cell carcinoma (RCC) is associated with greater risk of end-stage renal disease (ESRD). Patients and Methods We performed a population-based, retrospective cohort study using linked administrative databases in the province of Ontario, Canada. We included individuals with pathologically confirmed RCC diagnosed between 1995 and 2010. Cox proportional hazards, propensity score, and competing risks models were used to assess the impact of treatment choice. The primary outcome was ESRD. Secondary outcomes included overall mortality, myocardial infarction, and new-onset chronic kidney disease (CKD). A modern cohort of patients (2003–2010) was analysed separately. Results We included 11 937 patients, of whom 2107 (18%) underwent PN. The median follow-up was 57 months. In the full cohort, type of surgery was not associated with the rate of ESRD, whereas PN was associated with a decreased likelihood of ESRD compared with RN in the modern cohort using a multivariable proportional hazards model [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.25–0.75) or propensity score modelling (HR 0.48, 95% CI 0.27–0.82). PN was also associated with a lower risk of new-onset CKD (HR 0.48, 95% CI 0.41–0.57). Conclusions Although it is well-known that RN is associated with more CKD than PN, we provide the first direct evidence that PN is associated with less ESRD requiring renal replacement therapy than RN in a modern cohort of patients with RCC.

SummaryObjective Post-partum thyroiditis (PPT) is a common phenomenon in the general population. To date there have been few studies examining the incidence of PPT in women with hypothyroidism antedating pregnancy. This study aimed to assess the incidence and potential predictors of PPT in women with treated hypothyroidism antedating pregnancy. Design Retrospective cohort study. Patients and Methods We compiled a cohort of 97 women with previous hypothyroidism antedating pregnancy seen in the Endocrinology in Pregnancy clinic from 1999 to 2011, collecting data on thyroid function, antibodies and levothyroxine doses post-partum. The incidence of PPT and its predictors were analysed. Results A total of 66 (68%) women had fluctuations in thyroid function consistent with PPT. Of these, 22 (33%) had a hyperthyroid phase alone, 22 (33%) had a hypothyroid phase alone and 22 (33%) had both a hyper and hypo phase. The majority of women had their dose of thyroid medication adjusted during the PPT episode. Women who were on a full dose of thyroxine post-partum were significantly less likely to have a hypothyroid phase. In multivariable analysis, the only predictor of PPT was the presence of thyroid antibodies, with 83% of antibody positive women having PPT compared to 44% of antibody negative women (P = 0·0001). Conclusions In our cohort, 2/3 of women had fluctuations in thyroid function consistent with PPT and most required adjustment of their thyroid dose. Women with hypothyroidism antedating pregnancy are at high risk for PPT and should be closely monitored during the first year post-partum.

Fetal skeletal dysplasias are a heterogeneous group of rare genetic disorders, affecting approximately 2.4-4.5 of 10,000 births. We performed a retrospective review of the perinatal autopsies conducted between the years 2002-2011 at our center. The study population consisted of fetuses diagnosed with skeletal dysplasia with subsequent termination, stillbirth and live-born who died shortly after birth. Of the 2002 autopsies performed, 112 (5.6%) were diagnosed with skeletal dysplasia. These 112 cases encompassed 17 of 40 groups of Nosology 2010. The two most common Nosology groups were osteogenesis imperfecta [OI, 27/112 (24%)] and the fibroblast growth factor receptor type 3 (FGFR3) chondrodysplasias [27/112 (24%)]. The most common specific diagnoses were thanatophoric dysplasia (TD) type 1 [20 (17.9%)], and OI type 2 [20 (17.9%)]. The combined radiology, pathology, and genetic investigations and grouping the cases using Nosology 2010 resulted in a specific diagnosis in 96 of 112 cases.

Objective Epidemiologic assessments of sufficiently large populations are required in order to obtain robust estimates of disease prevalence and incidence, particularly when exploring the influence of various factors (age, sex, calendar time). We undertook this study to describe the epidemiology of rheumatoid arthritis (RA) over the past 15 years. Methods We used the Ontario Rheumatoid Arthritis administrative Database (ORAD), a validated population-based research database of all Ontarians with RA. The ORAD records were linked with census data to calculate crude and age and sex–standardized prevalence and incidence rates from 1996 to 2010. Vital statistics were used to estimate annual all-cause mortality during the study period. Results As of 2010, there were 97,499 Ontarians with RA, corresponding to a cumulative prevalence of 0.9%. Age and sex–standardized RA prevalence increased steadily over time from 473 (95% confidence interval [95% CI] 469–478) per 100,000 population (0.49%) in 1996 to 784 (95% CI 779–789) per 100,000 population (0.9%) in 2010. Age and sex–standardized incidence per 100,000 population ranged from 62 (95% CI 60–63) in 1996 to 54 (95% CI 52–55) in 2010. All-cause mortality decreased by a relative 21.4% since 1996. Conclusion Over a 15-year period, we observed an increase in RA prevalence over time. This rise may be attributed to the increasing time to ascertain cases (which may have been latent in the population during earlier years of the study), increasing survival, and/or an increase in the aging background population. Incidence appears to be stable.

Whole-body vibration (WBV) therapy has been proposed as a therapy to reduce sarcopenia and improve muscle strength. The purpose of this study was to explore whether 12 months of WBV therapy increases myotendinous density and volume of the distal tibia as measured by HR-pQCT in postmenopausal women in a parallel group, randomized controlled trial with 1:1:1 allocation to three arms. Postmenopausal women (N = 202) with low hip BMD were randomized to 20 min daily of 0.3g 30-Hz WBV therapy, 0.3g 90-Hz WBV therapy using the Juvent platform (Juvent, Somerset, NJ, USA), or no WBV. The main outcome measure was myotendinous density (HU) and volume (mm3) at the distal tibia measured at baseline and 12 months with HR-pQCT. There were no significant effects on myotendinous density or volume at the distal tibia after 12 months of daily 30- or 90-Hz WBV therapy compared with no WBV therapy. Mean change (SD) in myotendinous density from baseline was 4.6 (5.7) HU in the 30-Hz WBV group, 3.9 (6.1) HU in the 90-Hz WBV group, and 3.9 (5.4) HU in the control group (p = 0.70). Mean change (SD) in myotendinous volume from baseline was -7 (503) mm3 in the 30-Hz WBV group, 111 (615) mm3 in the 90-Hz WBV group, and 35 (615) mm3 in the control group (p = 0.50). In conclusion, WBV therapy at 30- or 90-Hz for 12 months had no significant effects on myotendinous density or volume at the distal tibia as measured by HR-pQCT in postmenopausal women. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Objective To determine expert beliefs regarding the probability of intestinal failure-associated liver disease (IFALD) with novel lipid-based approaches (lipid minimization/ω-3 lipids) in managing IFALD to facilitate Bayesian analyses of clinical trials of these therapies. Study design Structured interviews were conducted using a validated approach to belief elicitation with 60 intestinal failure (IF) experts from across North America. Participants were asked to estimate, in an average population of infants referred for management of IF with early IFALD, the probability of advanced IFALD at 3 months following referral in each of 3 scenarios: (1) conventional lipid, (2) ω-3 lipids, and (3) lipid minimization. Probability distributions of the risk of advanced IFALD with each strategy were developed. Distributions of the elicited treatment effect for the novel approaches, relative to conventional lipid, were calculated. Results Median duration of experience of participants managing patients with IF was 8.5 (range, 2-35) years. The median probability of advanced IFALD using conventional lipid was 32.5%; ω-3 lipids, 17.5%; and lipid minimization, 13%. The median of the elicited treatment effects relative to conventional lipid was a relative risk of 0.53 for the ω-3 lipid and 0.45 for lipid minimization. Conclusions There was consistent expert opinion that the novel lipid-based approaches are superior to conventional therapy, with similar estimates of treatment efficacy for the 2 approaches. The distributions of the elicited treatment effects can be used as prior distributions in Bayesian analyses of clinical trials of these novel strategies.

Summary. To explore the impact of the differences in baseline characteristics between immigrants with chronic hepatitis C (CHC) and native-born patients on the prognosis of advanced fibrosis. A retrospective cohort study was conducted in 318 patients (including 128 immigrants) with CHC and advanced fibrosis attending a tertiary referral clinic. Patients’ medical records were reviewed to collect data describing immigrant status, baseline characteristics, and liver-related clinical outcomes. Kaplan–Meier (KM) analyses and Cox proportional-hazards regression analyses were performed to explore the differences between the two groups with respect to clinical outcomes. Relative to native-born patients, immigrant patients were older, more likely to be female, and more likely to be Asian. Immigrants were less likely to be heavy drinkers, heavy smokers, injection drug users, and more likely to have type 2 diabetes. KM analyses indicated that immigrant patients had a significantly higher risk of hepatocellular carcinoma (HCC) than Canadian-born patients (P = 0.005). Univariate Cox proportional-hazards analyses indicated that immigrant status (hazard ratio (HR) 2.22; P = 0.006), age (HR 1.07; P

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? We know that a major benefit of partial nephrectomy (PN) over radical nephrectomy (RN) is greater preservation of kidney function. Emerging evidence also suggests that chronic kidney disease (CKD) correlates with survival, likely as a result of increased cardiovascular morbidity. We also know that Diabetes Mellitus (DM) followed by Hypertension (HTN) are the two most frequent causes of end-stage renal disease (ESRD). Given the strong association between renal functional decline and the surgical treatment of small renal masses, one would expect utilization of PN in patients with HTN or DM to be high, however minimal data exist on PN use in these populations. We are thus unable to determine whether these patients are being managed optimally. Our large study demonstrates that PN is being underutilized in patients at risk for CKD, particularly patients with Diabetes Mellitus and Hypertension. Unlike previously published reports, our population-level study provides a description of the landscape of care for patients with renal masses in general practice, and does not simply reflect treatment patterns at tertiary referral centers. The finding of low PN use in patients at risk for CKD deserves further study. Future studies should focus on determining the specific factors contributing to PN underutilization in these susceptible patients, as well as developing clinical tools to reliably identify those patients in whom the benefits of PN outweigh the risks. OBJECTIVE • To determine partial nephrectomy (PN) use in patients at risk of chronic kidney disease (CKD), such as those with diabetes mellitus (DM) and hypertension (HTN). PATIENTS AND METHODS • We conducted a national, population-based, retrospective, observational study using the Canadian Institute for Health Information Discharge Abstract Database. • We included all patients treated surgically for renal cell carcinoma from 1 April 1998 to 31 March 2008. • Patients with DM and HTN were identified using specific diagnosis codes. • The proportions of patients treated with PN were compared in patients with and without DM and HTN using multivariable logistic regression adjusting for covariates. RESULTS • A total of 24 579 patients were treated for a renal mass; of these, 4292 (17.5%) underwent PN. • In our sample, 5613 (22.8%) patients were identified as having HTN, and 2738 (11.1%) were identified as having DM. • PN was used in 17.3% of patients with HTN compared to 17.5% of those without HTN, whereas, in patients with DM, PN was used in 18.6% compared to 17.3% of patients without DM. • After adjusting for covariates, neither HTN, nor DM were found to be independently associated with increased PN use (odds ratio, 1.07; 95% CI, 0.98–1.16 and odds ratio, 1.08; 95% CI, 0.96–1.20, respectively). CONCLUSIONS • In this contemporary national analysis, PN appears to be underutilized in DM and HTN, despite their known relationship with chronic renal failure. • Further studies are needed to elucidate the specific factors contributing to PN underutilization in these susceptible patients.

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Androgen deprivation therapy was originally used for metastatic prostate cancer but is now used to treat all stages of the disease. Once considered to be relatively harmless, androgen deprivation therapy was associated with impaired cognitive function, anemia, loss of muscle strength, osteoporotic fractures, diabetes, and cardiovascular disease by the year 2000. In a large, population-based sample of prostate cancer patients, the numbers initiating androgen deprivation therapy increased from 1995 to 2001 and then sharply declined to 2005, but the rate of initiation among eligible prevalent cases steadily decreased over that period. Monotherapy with luteinizing hormone-releasing hormone agonists became the dominant type of androgen deprivation therapy. Changes may be related to fewer cases of late stage disease, potential adverse effects, and new evidence for selected indications and regimens. OBJECTIVE • To describe patterns of initiation of androgen deprivation therapy (ADT) in a population-based cohort of patients with prostate cancer. PATIENTS AND METHODS • All patients with prostate cancer in Ontario, Canada, who started ≥90 days of ADT at age ≥66 years in 1995–2005 were classified by ADT regimen: medical castration [oestrogen and/or luteinizing hormone-releasing hormone (LHRH) agonist); orchidectomy; antiandrogen monotherapy; combined androgen blockade (CAB) medical (medical castration plus antiandrogen); CAB surgical (orchidectomy plus antiandrogen). • Indications for ADT were as follows: neoadjuvant (short-term before prostatectomy or radiation therapy); adjuvant (long-term with prostatectomy or radiation therapy); metastatic disease; biochemical recurrence; primary (localized disease); other. • We examined trends in ADT regimen and indication over time. RESULTS • The number of patients initiating ADT increased from 1995 to 2001 (2106–2916 per year) and declined thereafter to 2200–2300 annually (total n= 26 809). • However, prostate cancer prevalence doubled over these years, and the rate of ADT initiation decreased from 16 to 7 per 100 person-years. • Patterns varied by regimen and indication. Medical castration increased from 12% of all ADT in 1995 to 47% in 2005; orchidectomy decreased from 17 to 4%. Use for metastatic disease remained stable, but adjuvant therapy increased from

Objective To determine the visualization rates of fetal anatomic structures by three-dimensional ultrasound (3DUS) at 12–13 weeks of gestation. Study Design This was a prospective observational study of women presenting for nuchal translucency ultrasound. Five 3D volumes of the fetus were acquired transabdominally. Two investigators independently reviewed the stored volumes offline following a standardized protocol. Results One hundred singleton fetuses were examined. The mean time for 3D volumes acquisition was 4.8 min; and for 3D review 17 min. Anatomic structures were seen as follows: cranium, lateral cerebral ventricles and abdominal wall 100%; stomach, vertebrae, upper and lower limbs ≥ 94%; face 71%, bladder 58%, both kidneys 39%, skin overlying spine 26% and heart 18%. Agreement between two observers ranged from 100% (for head, abdominal wall and lower limbs) to 43% (for visualization of skin overlying spine). A complete basic anatomic survey was achieved in 11.4% of the 12-week fetuses and 33.3% of the 13-week fetuses (p-value = 0.038). Conclusions First-trimester transabdominal 3DUS was adequate for assessment of the head, abdominal wall, stomach, limbs and vertebral alignment. It was less effective for evaluating the heart and intactness of the skin over the spine. Copyright © 2010 John Wiley & Sons, Ltd.

Purpose: To test the hypothesis that texture analysis of postcontrast T1-weighted MR images will predict hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) with better accuracy than visual evidence of contrast-enhancement (VE). Materials and Methods: Thirty-four AIS patients were examined within 3.5 ± 1.5 h after stroke. T1-weighted MR images were acquired 19 ± 7 min postcontrast injection. HT was determined by follow-up imaging at 24–72 h. Postcontrast images were evaluated for VE. Four second-order textural features were extracted (f1, f2, f3, and f9) for each patient. Receiver operating characteristic (ROC) curves were constructed for VE and for textural features, with HT as the outcome measure. Results: The f2 for HT patients (n = 12) was significantly lower than in non-HT patients (1058 ± 356 versus 1568 ± 527; P = 0.005); the converse was true for f3 (0.67 ± 0.12 versus 0.54 ± 0.13; P = 0.007). ROC analysis indicated that the f2 and f3 textural features were the only two significant predictors of HT (P = 0.0018 and P = 0.0042). The addition of VE to either f2 or f3 did not result in a significant improvement in accuracy. Conclusion: Texture analysis of postcontrast T1-weighted images may be superior to visual evidence of enhancement for the prediction of HT. J. Magn. Reson. Imaging 2009;30:933–941. © 2009 Wiley-Liss, Inc.

Aims Although a considerable body of research supports the efficacy of diabetes self-management education (DSME), these programmes are often challenged by high attrition rates. Little is known about factors influencing follow-up use of DSME services, thus the aim of this study was to identify these factors. Methods In this multisite prospective analysis, adults with Type 2 diabetes (n = 268) who attended one of two diabetes management centres (DMCs) were followed over a 1-year period from their initial visit. The influence of individual and contextual factors on the number of contacts with DMC providers was examined. Data were analysed within the context of the Health Behavioral Model of Health Services Utilization. Results In a multivariable negative binomial regression model, the number of contacts over 1 year was greater for those who were female, non-smokers, unemployed, self-referred to the DMC, lived closer to the DMC, had a lower body mass index, or had a longer known duration of diabetes. Follow-up use of services differed significantly between the two sites. Provider contacts were greater at the centre that offered flexible hours of services and a variety of optional educational modules. Conclusions Healthcare professionals need to encourage ongoing use of DSME, particularly for individuals prone to lower follow-up use of these services. Providing services that are accessible, convenient, and can easily fit into patients’ schedules may increase follow-up use. Further exploration into how operations and delivery of these services influence utilization patterns is strongly recommended.

OBJECTIVE To determine whether clinicians discuss bone-specific side-effects with patients on androgen-deprivation therapy (ADT) for prostate cancer, or prescribe lifestyle and pharmacological interventions for low bone mineral density (BMD), as decreased BMD is a common side-effect of ADT, leading to increased risk of fracture. PATIENTS AND METHODS Sixty-six men (mean age 70.6 years) with non-metastatic prostate cancer and starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual X-ray absorptiometry (DXA) at baseline. Patients were interviewed to obtain their medical histories, and charts were reviewed to determine whether clinicians documented potential bone side-effects in clinic notes, and made lifestyle and/or medication recommendations. Both were done at the start of ADT, and 3 and 6 months later. Patients were classified based on DXA T-score as having normal BMD, as osteopenic, or osteoporotic. RESULTS At baseline, 53% of patients had osteopenia and 5% had osteoporosis. Within 6 months of starting ADT, general side-effects and bone-specific side-effects of ADT were documented as being discussed with 26% and 15%, respectively. Clinicians recommended lifestyle interventions to 11% of patients. Pharmacological interventions (calcium, vitamin D, and/or bisphosphonates) were recommended to 18% of all patients within 6 months of starting ADT, and to 26% and 67% of osteopenic and osteoporotic patients, respectively. CONCLUSIONS A minority of patients is being informed of bone-specific side-effects of ADT. Lifestyle and drug interventions to prevent declines in BMD were recommended uncommonly. Practices around bone health for men starting ADT are suboptimal.

BACKGROUND. Comorbidity is an important consideration in oncology practice, particularly among older patients. Although a variety of comorbidity indices have been employed in research studies, it is unclear whether any one index is preferred. METHODS. An age-stratified random sample of 345 men (mean age of 69 years) who were newly diagnosed with prostate cancer were identified from a cancer registry in Ontario, Canada. Comorbidity and treatment information were obtained from chart review. Four comorbidity indices were utilized: Charlson Index, Diagnosis Count, Index of Coexistent Disease (ICED), and number of medications. Logistic regression analysis was used to compare the performance of comorbidity measures with respect to predicting receipt of curative treatment (radical prostatectomy or radiotherapy) and overall 6-year survival. Multivariable model performance including each of the comorbidity measures was compared by calculating the area under the receiver operating characteristic curve (AUROC). RESULTS. Among men with localized disease (n = 231), in models adjusted for age, Gleason score, and prostate-specific antigen level, only the Charlson Index was found to be a statistically significant predictor of receipt of curative treatment (P < .05), although all comorbidity indices had similar AUROC in adjusted models. After a median follow-up of 6.5 years, 116 of 345 men (33.6%) had died. In adjusted models, all 4 comorbidity indices performed similarly in predicting overall survival. CONCLUSIONS. Although comorbidity is an important predictor of both curative treatment and overall survival in prostate cancer, the optimal comorbidity index for use in research remains unclear. Selecting the optimal comorbidity index may depend on both the specific patient population and the outcome being considered. Cancer 2008. © 2008 American Cancer Society.

Background Our objective was to examine the construct validity of the Oral Mucositis Assessment Scale (OMAS) in children receiving doxorubicin chemotherapy. Methods Children between 6 and 18 years of age with cancer receiving doxorubicin-containing chemotherapy were included. OMAS was measured on days 7, 10, 14, and 17 after chemotherapy. Other measures of mucositis obtained concurrent with OMAS were the World Health Organization (WHO) mucositis scale and pain visual analogue scale (VAS). We also recorded analgesia administration. Results Sixteen children were studied for 45 post-chemotherapy cycles and 156 OMAS assessments were performed. OMAS was moderately correlated with WHO scores (r = 0.56; P = 0.0006) whereas correlation with the pain VAS was fair (r = 0.37; P = 0.002). OMAS also had fair correlation with the number of doses of topical analgesia (r = 0.43; P = 0.001) and with the cumulative dose of opioid analgesia (r = 0.38; P = 0.003). Conclusions The OMAS is valid for use in mucositis clinical trials for children at least 6 years of age. Pediatr Blood Cancer 2007;49:149–153. © 2006 Wiley-Liss, Inc.

BACKGROUND: Prophylactic platelet (PLT) transfusions are standard treatment for patients receiving high-dose chemotherapy, but the optimal dose is not known. A randomized controlled trial was undertaken to examine the effectiveness of low-dose PLT transfusions and to determine the need for further studies. STUDY DESIGN AND METHODS: Patients (n = 111) with acute leukemia or undergoing autologous peripheral blood progenitor cell (PBPC) transplantation were randomly assigned to receive low-dose (3 PLT units) or standard-dose (5 PLT units) prophylactic PLT transfusions and were monitored daily for bleeding. Using a sequential Bayesian design, the difference in major bleeding events was determined. RESULTS: The percentage of patients with major bleeding events was 10.7 percent (95% credible region, 5.1%-21.2%) in the low-dose PLT group and 7.3 percent (95% credible region, 2.9%-17.2%) in the standard-dose PLT group. The two additional events in the low-dose group occurred when the PLT count exceeded 100 × 109 per L. There is an 89 percent probability that the absolute increase in major bleeds is less than 10 percent with low-dose PLT transfusions. The number of minor bleeding events was higher in the standard-dose group. Patients receiving low-dose PLT transfusions received 25 percent fewer PLT units. There was an 89 percent probability that low-dose transfusions reduced PLT utilization in patients with acute leukemia and a 60 percent probability in patients undergoing PBPC transplantation. CONCLUSION: Low-dose PLT transfusions appear to be safe and effective and reduce PLT utilization. They should be further evaluated in clinical trials designed to evaluate equivalency.

Objectives: The objectives of this study are to identify the prevalence of depression and the accuracy of depression screening instruments in ambulatory head and neck cancer patients who have received radiation. This population is at risk for depression because of the life-threatening nature of the illness, and treatment-induced oral morbidity. Methods: Sixty subjects were evaluated for Major and Minor Depression according to Research Diagnostic Criteria using the Schedule for Affective Disorders and Schizophrenia (SADS). Screening instruments examined were the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS) and the Centre for Epidemiological Studies-Depression (CES-D) scale. Accuracy was assessed by calculating the sensitivities, specificities, positive predictive values (PPV) and areas under curve (AUC) from Receiver Operating Characteristic (ROC) curves. Results: The prevalence of Major and Minor Depression was 20%. All of the screening instruments tested were found to be highly accurate. Statistically significant differences between the instruments were not observed but the HADS demonstrated the highest absolute levels of sensitivity, specificity and PPV. No cases of Major Depression were missed by any of the instruments tested. Conclusions: These results suggest that a significant minority of head and neck cancer patients are depressed in the post radiation period, and that accurate screening for clinically significant depression is possible using any of the three instruments evaluated here. Copyright © 2003 John Wiley & Sons, Ltd.